Combination treatment for newly diagnosed AL amyloidosis

Daratumumab/Daratumumab and Hyaluronidase-fihj in Combination With Pomalidomide and Dexamethasone for the Treatment of Patients With Newly Diagnosed AL Amyloidosis: a Prospective, Multicenter, Single-arm Study

This study is testing a new combination treatment for people who have just been diagnosed with AL amyloidosis to see if it helps them feel better and improves their overall health.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Wenzhou Medical University (Academic / other)
• Drugs / interventions: daretozumab, Daratumumab
• Locations: 1 site (Wenzhou, Zhejiang)
• Trial ID: NCT06455748 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of a combination therapy involving Daratumumab, hyaluronidase-fihj, pomalidomide, and dexamethasone in patients newly diagnosed with AL amyloidosis. It is a prospective, single-arm study that aims to assess the hematologic overall remission rate and various secondary outcomes such as organ remission rates and progression-free survival. The study will also explore the safety profile of this combination therapy. Participants will be monitored for their response to treatment based on established guidelines.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with a confirmed diagnosis of primary AL amyloidosis and measurable disease.

Not a fit: Patients with severe organ dysfunction or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve remission rates and overall outcomes for patients with AL amyloidosis.

How similar studies have performed: While this approach is based on established therapies, the specific combination and its efficacy in AL amyloidosis is being explored, indicating a novel aspect of treatment.

Eligibility criteria

Inclusion Criteria:

1. Age: 18-80 years old, diagnosed with primary amyloidosis of AL tissue;
2. ECOG PS score 0-2 points;
3. Measurable disease: The difference between affected and unaffected FLC is\>20 mg/L, and the serum immunoglobulin kappa λ FLC ratio is abnormal;
4. Having sufficient organ and bone marrow function, defined as follows:

   1. Blood routine: Absolute neutrophil count ≥ 1.0 x 10 \^ 9/L, platelet count ≥ 50 x 10 \^ 9/L;
   2. Blood biochemistry and electrolytes: ALT and AST both ≤ 3 times the upper limit of normal, total bilirubin ≤ 1.5 times the upper limit of normal, creatinine clearance rate ≥ 30 mL/min, serum corrected calcium ≤ 14.0 mg/dL (≤ 3.5 mmol/L) or free ion calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L);
5. Women of childbearing age must agree to use contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study period and within 3 months after the end of the study; Within 7 days prior to enrollment in the study, the serum or urine pregnancy test was negative and must be a non lactating patient; In addition, if the subject misses their menstrual period or experiences abnormal menstrual bleeding, the researcher can conduct a pregnancy trial at any time during the study period;
6. Men must agree to use contraceptive measures during the study period and within 3 months after the end of the study period;
7. The patient agrees to participate in the clinical trial and signs an informed consent form.

Exclusion Criteria:

1. Non AL amyloidosis;
2. Known to be allergic, hypersensitive or intolerant to monoclonal antibodies or human derived proteins, daretozumab or its excipients, or known to be allergic to mammalian derivatives;
3. Female patients who have tested positive for lactation or serum pregnancy test during the screening period;
4. Received ASCT or had graft-versus-host disease in the past 12 months;
5. Suffering from moderate or severe persistent asthma within 2 years prior to enrollment, or having uncontrolled asthma at the time of enrollment;
6. Evidence of having other malignant tumors within the 3 years prior to enrollment or having been previously diagnosed with another malignant tumor with any residual lesions;
7. Suffering from chronic obstructive pulmonary disease (COPD), the forced expiratory volume (FEV1) in one second is less than 50% of the normal expected value;
8. Clinically significant heart disease, including:

   1. Start studying myocardial infarction or unstable or uncontrollable conditions within 6 months prior to treatment (such as unstable angina, congestive heart failure, New York Heart Association (NYHA) III-IV);
   2. Arrhythmias (NCI CTCAE V5.0 standard ≥ grade 3) or clinically significant electrocardiogram (ECG) abnormalities;
   3. The electrocardiogram shows a baseline corrected QT (QTc) interval\>470 ms;
9. Active infections, including but not limited to HAV, HBV, HCV, HIV;
10. Plasma cell leukemia (circulating plasma cells\>2.0 × 10 \^ 9/L) or Waldenstrom macroglobulinemia (WM) or POEMS syndrome (multiple neuropathies, organ enlargement, endocrine disorders, monoclonal plasma cell disease, and skin changes);
11. Peripheral neuropathy or neuralgia of grade 2 or above (CTCAE 5.0 standard);
12. Underwent major surgery within 14 days prior to enrollment, or did not fully recover from early surgery, or planned surgery during the study period or within 14 days after the last study drug treatment (note: does not include surgery under local anesthesia or kyphoplasty or vertebroplasty);
13. According to the judgment of the investigator, there are concomitant diseases (such as active systemic infection, uncontrolled diabetes, acute diffuse invasive pulmonary disease, neurological or mental disease, etc.) or any other conditions that may confuse the research results or affect the completion of the study;
14. Individuals who are receiving any other experimental drugs or experimental medical devices;
15. The researchers believe that the patient has other circumstances that are not suitable for participation in this study.

Where this trial is running

Wenzhou, Zhejiang

• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Yongyong Ma, MD — First Affiliated Hospital of Wenzhou Medical University
• Study coordinator: Yongyong Ma, MD

Conditions Amyloid Light-chain Amyloidosis